Complement mediated lysis of erythrocytes (E) is mediated by C5-C9, inserting into lipid bilayers of cell membranes. This requires binding and activation of C5 either by the classical or alternative pathway C5 convertases. We reported another mode of C5 activation which involves acidification to pH 6.4 of a mixture of C5 and C6. In the presence ofC7, C8 and C9, the neutralized mixture, designated C(56)a generates a lytic activity for chicken E. We have performed a comparative study of the biological behavior of C(56)a and C5b,6. It was found that C(56)a is similar to C5b,6 in several properties. We have extended these observations on the functional behavior of C(56)a and described some of the complexes physico-chemical properties. The acid generation of C(56)a is dose dependent with both C5 and C6 and is almost as efficient as classical or alternative pathway activation. While C(56)a decays in the present of C7 like C5b,6, the acid activated complex, in contrast to C5b,6 is also labile at 37 C in the absence of C7. Upon ultracentrifugation, acid activated C5 and C6 sediment consistent with the formation of a bimolecular 11S complex that coincides withthe appearance of lytic activity. Analysis of the chain structure of acid treated C5 obtained from Egp ghosts, demonstrates a C6 dependent, C5 chain cleavage.